Search PubMed⌕ Search

Biomedical subjects

D Richards

Publications and source records attributed to D Richards.

At least 109 records · Page 6Linked to original sources

Does post-withdrawal cue exposure improve outcome in opiate addiction? A controlled trial.

A controlled trial studied whether cue exposure prevented relapse in opiate addiction. Subjects were randomly allocated to one of two inpatient treatment settings: a drug dependence unit with a special 10 week program and 4 weeks in a behavioural/general treatment unit without such a program. In each setting, following drug-withdrawal, subjects had either cue exposure for at least six sessions over 3 weeks, or a control condition. Subjects were followed up twice, at about 6 weeks and 6 months post-treatment. 186 subjects were randomly allocated; 69 were assessed post-detoxification, and of these 43 completed cue exposure or control treatments. Cue exposure and control subjects did not differ in cue reactivity. This was evaluated post-treatment for cue exposure subjects and at a comparable time point for controls. All groups showed a significant decrement in cue-elicited craving, withdrawal responses and negative mood. Cue exposure and control subjects did not differ at either of the two follow up interviews.

Adult↗

Biochemical parameters of recovery in acute severe head injury.

Levels of urinary catecholamines (noradrenaline, adrenaline, dopamine), plasma acetylcholinesterase, serum serotonin and plasma 3-methoxy-4-hydroxyphenylglycol were recorded in 38 adult subjects during the first 21 days after severe head injury. Levels of acetylcholinesterase, serotonin and 3-methoxy-4-hydroxyphenylglycol differed significantly between survivors and those who died. For survivors, initially abnormal biochemical levels recovered toward the norm as time after injury progressed.

Acetylcholinesterase↗

Clinical audit of behaviour therapy training of nurses.

In health care training, professional examinations of competence test trainees' knowledge rather than their actual contribution to the improvement of patients' health. Clinical training programmes have the ultimate aim of improving patients' health, but rarely measure their success in attaining it. This paper provides an analysis of the results of clinical outcome for 2,032 patients treated during eight consecutive English National Board 650 courses, in which 68 nurse behaviour therapist trainees were trained at the Maudsley Hospital from 1978-91. The outcome of 668 patients treated in three recent courses (1987-91) is compared with that of 1,384 patients treated in five earlier courses (1978-86). Measures and diagnostic categories were similar over the whole study period. The trainees in 1987-91 achieved a similar health gain for most of their patients as did their counterparts in 1979-86, but this was achieved over a shorter time spent with each patient, and with greater effect in patients diagnosed as obsessive ruminators. These efficiency gains seem to reflect the incorporation into recent training of treatment advances in anxiety disorders.

Behavior Therapy↗

One simple change.

Explore the source record for details and available documents.

General Practice, Dental↗

Modulation of monocyte functions by muramyl tripeptide phosphatidylethanolamine in a phase II study in patients with metastatic melanoma.

BACKGROUND: Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic analogue of muramyl dipeptide (MDP), a component of bacterial cell walls that has potent in vitro monocyte-activating properties. We conducted a phase II clinical trial of MTP-PE in 30 patients with metastatic melanoma. PURPOSE: Our purpose was to define a clinical response rate for this agent in patients with advanced melanoma and to evaluate the agent's immunomodulatory properties. METHODS: Patients were randomly assigned to 1- or 4-mg dose levels of MTP-PE and received the drug intravenously once a week for 12-24 weeks. Immunological monitoring consisted of measurement of plasma tumor necrosis factor-alpha (TNF-alpha), neopterin, interleukin-1-beta, interleukin-6 (IL-6), and beta 2-microglobulin levels; phenotyping analysis of expression of human HLA-DR, CD-14 on mononuclear cells; and measurement of in vitro monocyte cytotoxicity against SKMel28 targets cells. RESULTS: MTP-PE was well tolerated; fever and chills were the major toxic effects. Plasma TNF-alpha levels increased 16-fold 2 hours after the first MTP-PE treatment. Increases in TNF-alpha levels after MTP-PE administration continued through week 12, but changes were of a lower magnitude after week 1. Plasma neopterin levels were significantly increased 24 hours after treatment at weeks 1, 6, and 12. A marked increase in IL-6 and a modest rise in beta 2-microglobulin levels were also seen at week 1. No significant changes from baseline IL-1 beta were observed. In the cytotoxicity assay, monocyte cytotoxic activity was significantly increased at weeks 4 and 6. Surface immuno-phenotyping revealed a consistent transient reduction in the number of circulating monocytes 2 hours after MTP-PE was administered. In addition, we observed a down-regulation (i.e., a decrease) in the expression of Leu M3 and HLA-DR on monocytes, 2 hours after MTP-PE treatment, followed by a recovery 24 hours after treatment. No objective clinical responses were seen in this advanced disease population. CONCLUSIONS: We conclude that MTP-PE has pleiotropic and potentially beneficial biologic effects and that further clinical investigations of MTP-PE are justified. IMPLICATIONS: In view of the clear immunomodulatory actions seen in our study and in earlier clinical trials, we believe that MTP-PE deserves further study in the adjuvant setting.

Acetylmuramyl-Alanyl-Isoglutamine↗

The detection of IgE-secreting cells in the peripheral blood of patients with atopic dermatitis.

We report, for the first time, the identification of IgE-secreting cells in human peripheral blood with an ELISA plaque assay that detects the fingerprint of individual IgE-secreting cells. No IgE-secreting cells could be detected in the blood of normal individuals (IgE, less than 100 IU/ml) or atopic patients (IgE, less than 1000 IU/ml), but in patients with atopic dermatitis (AD) whose IgE was greater than 2000 IU/ml, there was an average of 49 +/- 9 IgE-secreting cells per 10(6) peripheral blood mononuclear cells (PBMNCs). The rate of IgE production per cell per day from the PBMNCs of patients with AD varied from 0.051 to 0.628 IU/ml, and the number of IgE-secreting cells was positively correlated with the serum-IgE levels of these subjects (r = 0.74; p less than 0.001) and the amount of IgE detected in the culture supernatant (r = 0.085; p less than 0.02). Secretion of IgE by these cells could be completely inhibited (96.2% +/- 3%) by the addition of 75 micrograms of cyclohexamide to the cultures. Preformed intracellular IgE comprised 10% of the IgE detected in the supernatants of 7-day cultures. PBMNCs from patients with AD depleted of monocytes by adherence and T cells by E rosetting, all contained some detectable IgE-secreting cells, whereas isolated T cells and monocytes did not, supporting the view that cells secreting IgE that were detected were indeed B cells.

Antibody-Producing Cells↗

Correlation between tumor necrosis factor-alpha (TNF-alpha)-induced cytoskeletal changes and human collagenase gene induction.

Tumor necrosis factor-alpha (TNF-alpha) has been shown not only to induce the biosynthesis and secretion of collagenase but also to change the organization of cytoskeletal components. In the present study we explore the correlation between the biosynthesis of collagenase (by mRNA hybridization, indirect immunofluorescence and collagenolytic activity), and cytoskeletal reorganization (by rhodamine-phalloidin staining of F-actin) induced in fibroblasts by recombinant TNF (rTNF). In the concentration range of 1-100 ng/ml, rTNF increased extracellular collagenase activity 8-fold and collagenase mRNA 4-fold. In addition, whereas the collagenase mRNA was detected as early as 24 h posttreatment, the appearance of extracellular collagenase activity required 48 h. Using phalloidin to follow the organization of the cytoskeleton we observed that rTNF disrupted the parallel array of stress fibers normally observed in the perinuclear region. In contrast to the time required to affect collagenase synthesis, the effect of rTNF on stress fiber organization occurred as early as 6 h post-treatment. Finally, while the number of cells exhibiting this change increased with increasing concentrations of rTNF, a maximum of about 30% of the cells showed this effect. Interestingly, double staining studies demonstrated that both stress fiber changes and procollagenase production occurred in the same cells. This finding, together with the observation that the cytoskeletal disorganization preceded collagenase gene induction by at least 18 h is consistent with the conclusion that the organizational status of the microfilaments may have a role as a regulator of procollagenase gene expression.

Actin Cytoskeleton↗

Relation of pyloric motility to pyloric opening and closure in healthy subjects.

The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and a sleeve sensor positioned astride the pylorus. Simultaneous with manometry, pyloric opening and closure and antroduodenal contractions were observed fluoroscopically with the antrum filled with barium. During intraduodenal normal saline infusion, coordinated antral pressure waves swept over the pylorus and ejected barium into the duodenum. No localised pyloric motor pattern was observed under these conditions. In contrast, the intraduodenal triglyceride infusion was associated with the absence of antral pressure waves and virtual absence of antral wall movement. At the pylorus, there was a zone of luminal occlusion less than 1 cm long that persisted for the period of observation. This zone of luminal occlusion corresponded precisely with manometric recordings of a narrow zone of pyloric phasic and tonic activity. During the duodenal triglyceride infusion, the pylorus was closed for 98.5% of the measurement period when basal pyloric pressure was 4 mm Hg or more, and during this motor pattern, barium did not traverse the pylorus. Localised pyloric contractions cause sustained pyloric closure, whether these contractions are phasic or tonic. These contractions occur independently of antral or duodenal contractions and may interrupt gastric emptying.

Adult↗

Independent evaluation of impotence by colour Doppler imaging and cavernosometry.

Colour Doppler imaging and cavernosometry are the optimal means for objective assessment of pharmacologically induced penile erections. 21 impotent patients were assessed by both methods independent of the information derived from the other modality. The diagnosis obtained was found to be immediately consistent in only 10 cases, 7 of which had venous leakage. 6 of the remaining 11 patients had a diagnosis of mixed arterial and venous disease in one or the other modality, but only arterial or venous disease alone in the other. The remaining 5 patients had completely inconsistent diagnoses. However, knowledge of the clinical picture and awareness of the pitfalls in the diagnostic procedures allows most of the discrepancies to be explained. Colour Doppler imaging is subject to operator error but allows selection of patients for cavernosography.

Erectile Dysfunction↗

Exertion-induced heat exhaustion. An often overlooked diagnosis.

Exertion-induced heat exhaustion is a potentially lethal condition. The earliest signs include unsteady gait and confusion. Recording of rectal temperature is essential. Skin colour, blood pressure and heart rate are not reliable diagnostic signs. The mainstays of therapy are rapid rehydration and cooling. Prompt diagnosis and rapid effective therapy will minimise the risk of death.

Adult↗

The IgE and IgG subclass antibody response to foods in babies during the first year of life and their relationship to feeding regimen and the development of food allergy.

This follow-up study of 191 babies investigated the development of food allergy in an unselected population and its relationship to total and antigen-specific IgE and IgG subclass levels. Sensitization to egg, as indicated by a positive skin test or RAST, was found in 5% of 1-year-old babies, but none of the babies in this series fulfilled the clinical criteria for immediate-type milk allergy. For both bovine casein (CAS) and egg albumin, the IgG response was largely restricted to IgG1 in contrast to the predominant IgG4 response to these antigens that is found in adults. The level of IgG4, but not IgG1, antibody to CAS and ovalbumin (OV) was lower in some of the babies compared with that of their mothers (N = 166; p less than 0.05, Student's paired t test). However, there was no difference in the total serum IgG subclass levels between mothers and babies. These results demonstrate that, in the population of babies studied, (1) type I hypersensitivity to egg occurred in 5% of 1-year-old babies, (2) the predominant IgG subclass of antibodies to CAS and OV in babies is IgG1, and (3) in the 22% of babies, there was substantially (greater than 1000-fold) less IgG4 antibody to CAS and OV than in their mothers, suggesting specific exclusion of some IgG4 antibodies.

Antibody Specificity↗

Neonatal IgE: a poor screen for atopic disease.

Screening for atopic disease using neonatal serum IgE has been advocated on the basis of the predictive value of elevated levels. However, this is only one measure of validity. The test was validated fully in 92 infants with a bi-parental history of atopy using 0.7 IU/ml as the cut-off. All infants were assessed prospectively for evidence of atopic disease (eczema, recurrent wheezing or food reactions) and skin-prick test positivity in the first year. Total serum IgE was measured by ultrasensitive ELISA on 61 cord blood samples and 92 samples taken at 7 days. All cord samples were re-analysed by PRIST and the first 33 by ultrasensitive RIA giving, respectively, 82% and 94% concordance (regarding undetectable, detectable and elevated levels) with ELISA. Maternal contamination was indicated in 7% of cord samples by high serum IgA. Ninety-five per cent of cord/7-day IgE pairs showed no change or minor rises at 7 days. Forty-nine per cent of the infants had evidence of atopic disease. Only 5% had elevated 7-day IgE. The positive and negative predictive values of the 7-day test were 60% and 52%, respectively, and specificity 96% but the sensitivity was only 7%. High levels did not distinguish the infants with the most unequivocal evidence of disease, i.e. eczema with a positive skin test. In conclusion IgE at 7 days is comparable to and more reliable than cord IgE. However, neonatal IgE screening is too insensitive to have clinical application.

Enzyme-Linked Immunosorbent Assay↗